Skip to main content
Log in

Effect of PGML Excipient Mixture in a Transdermal System on the in Vitro Transport of Estradiol Across Skin

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. To measure the effect of a combination of excipients from a silicone based pressure sensitive adhesive (PSA) on drug transport across skin.

Methods. Partitioning of propylene glycol monolaurate (PG-ML) from silicone PSA and a solution formulation into the stratum corneum (SC) was measured using radiolabeled PG-ML. Transport of a model drug, estradiol, as well as PG-ML across skin were measured in vitro using heat separated epidermis from human cadaver skin.

Results. The PG-ML partitioning into SC showed a saturation and was independent of the formulation. The local dielectric of the lipid bilayers of the SC showed an increase as a result of PG-ML uptake, as determined by the decrease in fluorescence lifetime of a lipophilic probe incorporated into the SC. However, there was no alteration of lipid packing in SC.

Conclusions. The PG-ML and estradiol transport showed a good correlation over 3 days, suggesting that the two species are co-transported across the epidermis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Y. W. Chien. Transdermal Controlled Systemic Medication, Dekker, New York, 1987.

    Google Scholar 

  2. I. H. Blank. Cutaneous barriers. J. Invest. Dermatol. 45:249–256 (1965).

    Article  CAS  PubMed  Google Scholar 

  3. A. G. Matoltsy, A. M. Downes, and T. M. Sweeney. Studies of the epidermal water barrier. Part II. Investigation of the chemical nature of the water barrier. J. Invest. Dermatol. 50:19–26 (1968).

    Google Scholar 

  4. K. A. Walters and J. Hadgraft. Pharmaceutical Skin Penetration Enhancement, Marcel Dekker, Inc., New York, 1993.

    Google Scholar 

  5. B. W. Barry. Mode of action of penetration enhancers in human skin. J. Control. Rel. 6:85–97 (1987).

    PubMed  Google Scholar 

  6. K. A. Walters. Penetration enhancers and their use in transdermal therapeutic systems, in “Transdermal Drug Delivery”, J. Hadgraft and R. H. Guy, Eds., Marcel Dekker, New York 1989.

    Google Scholar 

  7. A. F. Kydonieus. Fundamentals of transdermal drug delivery, in “Transdermal Drug Delivery”, vol. 1, A. F. Kydonieus and B. Berner, Eds., CRC Press, Boca Raton, Florida, 1987.

    Google Scholar 

  8. M. C. Math and H. Saunal. Combined effect of propylene glycol and propylene glycol monolaurate on the transport of estradiol through human skin, in “Prediction of Percutaneous Penetration”, vol. 3b, K. R. Brain, V. J. James, and K. A. Walters, Eds., STS Publishing, Cardiff, UK, 1993.

    Google Scholar 

  9. G. W. Cleary and S. D. Roy. Transdermal drug delivery composition. US Patent # 4906463 (1990).

  10. M. D. Garrison, L. M. Doh, R. O. Potts, and W. Abraham. Effect of oleic acid on human epidermis: Fluorescence spectroscopic investigation. J. Control. Rel. 31:263–269 (1994).

    Google Scholar 

  11. D. M. Jameson, E. Gratton, and R. D. Hall. The measurement and analysis of heterogeneous emissions by multifrequency phase and modulation fluorometry. Applied Spectros. Rev. 20:55–106 (1984).

    Google Scholar 

  12. J. R. Lakowicz, H. Cherek, B. P. Maliwal, and E. Gratton. Time-resolved fluorescence anisotropies of diphenylhexatriene and perylene in solvents and lipid bilayers obtained from multifrequency phase-modulation fluorometry. Biochemistry 24:376–383 (1985).

    Google Scholar 

  13. M. Goodman and B. W. Barry. Lipid-Protein-Partitioning (LPP) theory of skin enhancer activity: finite dose technique. Int. J. Pharm. 57:29–40 (1989).

    Google Scholar 

  14. K. A. Walters and J. Hadgraft. Pharmaceutical Skin Penetration Enhancement, Marcel Dekker, Inc., New York, 1993, p. 176.

    Google Scholar 

  15. G. M. Gray, R. J. White, R. H. William, and H. J. Yardley. Lipid composition of the superficial stratum corneum cells of pig epidermis. Br. J. Dermatol. 106:59–63 (1982).

    Google Scholar 

  16. B. R. Lentz, Y. Barenholz, and T. E. Thompson. Fluorescence depolarizarion studies of phase transitions and fluidity in phospholipid bilayers, 2. Two-component phosphatidylcholine liposomes. Biochemistry 15:4529–4536 (1976).

    Google Scholar 

  17. P. W. Wertz and D. T. Downing. Ceramides of pig epidermis: structure determination. J. Lipid Res. 24:759–765 (1983).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Irion, G.D., Garrison, M.D. & Abraham, W. Effect of PGML Excipient Mixture in a Transdermal System on the in Vitro Transport of Estradiol Across Skin. Pharm Res 12, 1618–1622 (1995). https://doi.org/10.1023/A:1016232831431

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1016232831431

Navigation